As a candidate, I have a longstanding interdepartmental collaboration between the departments of Medicine and Obstetrics and Gynecology with a long-term goal to become an independent researcher in gestational diabetes (GDM) and placental hormone physiology. The K-23 Award would allow me to combined clinical research skills I have gained by attaining my MSPH degree and basic research skills I am obtaining through my endocrinology fellowship in order to become a productive clinical investigator. My proposed patient oriented research focuses on the mechanisms of abnormal insulin signaling in GDM and the role of placental hormones in causing the insulin resistance of pregnancy. This award would allow me to gain expertise in executing patient oriented research on the Adult GCRC. The goal of this proposed longitudinal research project is to define the underlying abnormalities in insulin signaling in women with gestational diabetes, determine whether these abnormalities persist in women with normalize their glucose tolerance postpartum versus those who do not, and determine the placental hormones responsible for causing the insulin resistance of pregnancy. Gestational diabetes (GDM) complicates 3-10% of all pregnancies and is increasing in incidence, yet little is known about the molecular mechanisms of the insulin resistance. It results in significant morbidity to both the mother and the fetus, including a 50% risk of developing Type 2 DM in the mother, and a high prevalence of childhood obesity and adult DM in the offspring. This research would examine mechanisms of insulin resistance in others with GDM compared to pregnant controls by studying abnormalities in insulin signaling in skeletal muscle in a longitudinal prospective manner. This would be achieved by obtaining muscle biopsies before and after an oral glucose load in these two groups of women at 24-32 weeks of pregnancy. In order to examine whether or not these abnormalities persist postpartum, repeat muscle biopsies will be taken at 8-12 weeks postpartum before and after the same glucose load. Women with history of GDM who normalize their glucose tolerance will be compared to those who continue to have impaired glucose tolerance postpartum. Lastly, the cause of the insulin resistance in pregnancy will be examined by exposing muscle fibers taken at elective abdominal surgeries in non- pregnant women to placental hormones, including human placental growth hormone and human placental lactogen. This will determine whether the in-vivo insulin signaling abnormalities can be recreated in vitro with placental hormones individuals or in combination. Identifying the abnormalities in insulin signaling in this high risk population as well as the role of placental hormones in mediating the insulin resistance of pregnancy is critical so that progress can ultimately be made towards the prevention of Type 2 diabetes in the mother as well obesity and glucose tolerance in her offspring.